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// ═══════════════════════════════════════════════════════════════════════════
// SLIDE 1 — TITLE
// ═══════════════════════════════════════════════════════════════════════════
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// ═══════════════════════════════════════════════════════════════════════════
// SLIDE 2 — OUTLINE
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// ═══════════════════════════════════════════════════════════════════════════
// SECTION 1 — INTRODUCTION
// ═══════════════════════════════════════════════════════════════════════════
sectionDivider("01  Introduction to Autocoids", "Local hormones acting near their site of synthesis");

contentSlide("What are Autocoids?", [
  "Derived from Greek: autos (self) + akos (remedy/drug) — coined by Sir Edward Schafer",
  "Biologically active substances synthesised locally and act near their site of production (paracrine/autocrine)",
  "Also called local hormones or autopharmacological agents",
  "NOT transported via blood to distant organs (unlike classical hormones)",
  "Act through specific receptors to mediate physiological & pathological responses",
  "Released in response to: tissue injury, inflammation, allergic reactions, nerve stimulation",
  "Can be rapidly inactivated — very short half-lives (seconds to minutes)",
  "Major classes: Biogenic amines (histamine, serotonin), Eicosanoids, Kinins, Neuropeptides, Platelet-activating factor (PAF)",
]);

contentSlide("Classification of Autocoids", [
  "1. Biogenic Amines",
  { text: "Histamine — stored in mast cells & basophils; released in allergy & inflammation" },
  { text: "Serotonin (5-HT) — gut, platelets, CNS; roles in mood, vascular tone, GI motility" },
  "2. Eicosanoids (derived from arachidonic acid)",
  { text: "Prostaglandins (PGs), Thromboxanes (TXs), Leukotrienes (LTs), Lipoxins" },
  "3. Kinins",
  { text: "Bradykinin, Kallidin — potent vasodilators, pain mediators" },
  "4. Neuropeptides",
  { text: "Substance P, Neurotensin, Calcitonin Gene-Related Peptide (CGRP)" },
  "5. Others",
  { text: "Platelet-Activating Factor (PAF), Adenosine, Nitric Oxide (NO), Endothelins" },
]);

// ═══════════════════════════════════════════════════════════════════════════
// SECTION 2 — HISTAMINE
// ═══════════════════════════════════════════════════════════════════════════
sectionDivider("02  Histamine", "Synthesis · Storage · Receptors · Organ Effects");

contentSlide("Histamine – Chemistry & Synthesis", [
  "Chemical name: 2-(4-imidazolyl)ethylamine — derived from the amino acid L-Histidine",
  "Synthesis: L-Histidine → Histamine via Histidine decarboxylase (pyridoxal phosphate dependent)",
  "Storage: Bound to heparin-protein complexes in mast cell and basophil granules",
  "Also found in: enterochromaffin-like (ECL) cells of gastric mucosa, neurons in brain, platelets",
  "Release triggers: Antigen–IgE interaction (Type I hypersensitivity), drugs (morphine, tubocurarine, vancomycin), trauma/heat, basic polypeptides, complement (C3a, C5a)",
  "Metabolism: Methylation by N-methyltransferase OR oxidative deamination by diamine oxidase (DAO)",
  "Main metabolites: N-methylimidazoleacetic acid, Imidazoleacetic acid (excreted in urine)",
  "Endogenous histamine half-life: seconds to minutes",
]);

tableSlide("Histamine Receptors – Summary",
  ["Receptor", "Coupling", "Location", "Key Effects"],
  [
    ["H1", "Gq/PLC → IP3/DAG, ↑Ca²⁺", "Smooth muscle, endothelium, nerve endings, CNS", "Bronchoconstriction, vasodilation (NO), ↑vascular permeability, itch, pain, wakefulness"],
    ["H2", "Gs → ↑cAMP", "Gastric parietal cells, cardiac muscle, smooth muscle, immune cells", "↑Gastric acid secretion, cardiac stimulation, vasodilation (high-dose)"],
    ["H3", "Gi → ↓cAMP, ↓Ca²⁺ in nerve terminals", "Presynaptic: brain, peripheral nerves (autoreceptor)", "↓Histamine release, ↓release of ACh/NA/5-HT/GABA; modulates appetite & sleep"],
    ["H4", "Gi → ↓cAMP", "Bone marrow, eosinophils, mast cells, leukocytes", "Chemotaxis of eosinophils & mast cells, cytokine production, allergy & inflammation"],
  ],
  C.bg_mid
);

contentSlide("Histamine – Organ System Effects", [
  "CVS: ↓BP (arteriolar dilation via H1+H2), ↑HR (direct H2 + reflex), flushing, headache; H1 → NO-mediated vasodilation",
  "Respiratory: H1-mediated bronchoconstriction; ↑bronchial secretions; NOT significant in healthy humans but pronounced in asthmatics",
  "GI: H2 → ↑gastric acid & pepsin secretion; H1 → smooth muscle contraction (cramps, diarrhea)",
  "Skin: Triple Response of Lewis — red flare (arteriolar dilation), wheal (↑permeability), flare (axon reflex); urticaria, itch, pain",
  "Nervous system: Stimulates sensory nerve endings → itch & pain; H3 receptors modulate neurotransmitter release; H1/H3 regulate appetite",
  "Glands: ↑ secretion from salivary, lacrimal, bronchial glands",
  "Systemic release: Anaphylaxis → severe ↓BP, bronchospasm, angioedema",
]);

contentSlide("H1 Antihistamines – First Generation", [
  "Mechanism: Competitive, reversible H1-receptor inverse agonists (stabilise inactive conformation)",
  "Cross the blood–brain barrier → CNS sedation (H1 block in brain), anticholinergic effects",
  "Structural classes & examples:",
  { text: "Ethanolamines: Diphenhydramine, Dimenhydrinate, Clemastine — most sedating" },
  { text: "Ethylenediamines: Tripelennamine, Pyrilamine — moderate sedation" },
  { text: "Alkylamines: Chlorpheniramine, Brompheniramine — less sedating, most widely used" },
  { text: "Piperazines: Cyclizine, Meclizine, Hydroxyzine — anti-motion-sickness, anti-emetic" },
  { text: "Phenothiazines: Promethazine — strongly sedating, anti-emetic, H1+D2 block" },
  { text: "Piperidines: Cyproheptadine — also 5-HT antagonist; used in appetite stimulation" },
  "Onset: 15–30 min oral; Duration: 4–6 h; Metabolism: hepatic (CYP)",
]);

contentSlide("H1 Antihistamines – Second Generation", [
  "Key feature: Do NOT cross BBB → minimal sedation; no significant anticholinergic effects",
  "High peripheral H1 selectivity; some have additional anti-inflammatory actions",
  "Drugs: Loratadine, Desloratadine, Cetirizine, Levocetirizine, Fexofenadine, Azelastine (topical), Olopatadine",
  "Loratadine: Prodrug → desloratadine; once daily; mild anti-inflammatory (↓ mast cell mediators)",
  "Cetirizine: Metabolite of hydroxyzine; most potent; slight sedation at high doses (P-gp substrate poor)",
  "Fexofenadine: P-gp substrate → minimal CNS penetration; safest for pilots/operators",
  "Clinical uses: Allergic rhinitis (2nd line after intranasal corticosteroids), chronic urticaria, atopic dermatitis (adjunct), allergic conjunctivitis (topical azelastine/olopatadine)",
  "Note: Sedation occurs in ~7% with 2nd-gen vs ~50% with 1st-gen agents",
]);

twoColSlide(
  "1st Gen vs 2nd Gen H1 Antihistamines",
  "1st Generation",
  [
    "Cross BBB → sedation, cognitive impairment",
    "Anticholinergic: dry mouth, urinary retention, blurred vision, constipation",
    "Antiemetic & anti-motion sickness",
    "Short duration (4-6h) → multiple daily doses",
    "Cheap, OTC available",
    "Contraindicated: BPH, narrow-angle glaucoma",
    "Examples: Diphenhydramine, Chlorpheniramine, Promethazine",
  ],
  "2nd Generation",
  [
    "Do NOT cross BBB → non/minimally sedating",
    "No anticholinergic effects",
    "Longer duration (12-24h) → once daily dosing",
    "Some inhibit mast cell degranulation (additional anti-inflammatory)",
    "More expensive",
    "Safe in elderly, drivers, operators",
    "Examples: Loratadine, Cetirizine, Fexofenadine, Desloratadine",
  ]
);

contentSlide("H2 Receptor Antagonists", [
  "Mechanism: Competitive H2-receptor blockers → ↓gastric acid secretion (both basal & stimulated)",
  "Drugs: Cimetidine, Ranitidine*, Famotidine, Nizatidine (*ranitidine withdrawn due to NDMA contamination)",
  "Cimetidine: First clinically useful H2 blocker; inhibits CYP1A2, CYP2C9, CYP3A4 → multiple drug interactions; antiandrogenic effects (gynecomastia, ↓libido)",
  "Famotidine: Most potent; no CYP inhibition; no antiandrogenic effects; preferred in practice",
  "Nizatidine: Similar to ranitidine; 100% bioavailability",
  "Clinical uses: Peptic ulcer disease, GERD, Zollinger-Ellison syndrome (combined with PPI), prevention of stress ulcers",
  "Adverse effects: Generally well tolerated; headache, diarrhea, constipation; cimetidine: confusion in elderly, drug interactions",
  "Note: Largely replaced by PPIs for acid suppression but used for urticaria and pruritus",
]);

// ═══════════════════════════════════════════════════════════════════════════
// SECTION 3 — SEROTONIN
// ═══════════════════════════════════════════════════════════════════════════
sectionDivider("03  Serotonin (5-HT)", "Synthesis · Receptors · Clinical Pharmacology");

contentSlide("Serotonin – Chemistry & Synthesis", [
  "Chemical name: 5-Hydroxytryptamine (5-HT); indolamine derived from L-Tryptophan",
  "Synthesis pathway: L-Tryptophan → 5-Hydroxytryptophan (via Tryptophan hydroxylase-1, rate-limiting) → Serotonin (via AADC/decarboxylase)",
  "Distribution: >90% in enterochromaffin cells of GI tract; CNS raphe nuclei; platelets (storage, NOT synthesis)",
  "Pineal gland: serotonin precursor to Melatonin (via AANAT + ASMT)",
  "Storage & transport: SERT (serotonin transporter) on platelets & neurons; VAT (vesicular amine transporter) in vesicles",
  "Reserpine depletes 5-HT by blocking VAT (also depletes catecholamines)",
  "Metabolism: Mainly by MAO → 5-hydroxyindoleacetaldehyde → 5-HIAA (5-hydroxyindoleacetic acid); urinary 5-HIAA elevated in carcinoid syndrome",
  "Measurement: Urinary 5-HIAA: marker for carcinoid tumor activity",
]);

tableSlide("Serotonin Receptor Classification",
  ["Receptor", "Mechanism", "Location", "Function / Clinical Relevance"],
  [
    ["5-HT1 (A,B,D,E,F)", "Gi → ↓cAMP", "CNS (limbic, raphe), blood vessels", "Presynaptic autoreceptors; vasoconstriction; 5-HT1A: anxiety/depression (buspirone); 5-HT1B/D: migraine (triptans); 5-HT1F: migraine (lasmiditan)"],
    ["5-HT2 (A,B,C)", "Gq → ↑IP3/DAG, ↑Ca²⁺", "CNS, platelets, smooth muscle, endothelium", "Vasoconstriction, platelet aggregation, GI contraction, hallucinations (2A); appetite (2C); 5-HT2 blocked by atypical antipsychotics & cyproheptadine"],
    ["5-HT3", "Ion channel (Na⁺/K⁺)", "Peripheral/central neurons, GI tract, CTZ", "Depolarisation → nausea/vomiting, pain; blocked by ondansetron, granisetron (antiemetics)"],
    ["5-HT4", "Gs → ↑cAMP", "GI tract (enteric neurons), CNS, heart", "↑GI motility, ↑ACh release; cisapride (withdrawn), metoclopramide (partial), prucalopride"],
    ["5-HT6, 5-HT7", "Gs → ↑cAMP", "CNS (striatum, hippocampus, thalamus)", "Cognition, sleep, mood; targets for antipsychotics (clozapine, olanzapine block 5-HT7)"],
  ],
  C.accent1
);

contentSlide("Serotonin Agonists – Clinical Use", [
  "TRIPTANS (5-HT1B/D agonists) — Acute migraine",
  { text: "Sumatriptan (SC/oral/nasal/rectal), Zolmitriptan, Rizatriptan, Eletriptan, Almotriptan, Frovatriptan, Naratriptan" },
  { text: "Mechanism: Activate 5-HT1B (cranial vasoconstriction) + 5-HT1D (↓trigeminal nociceptive transmission + CGRP release)" },
  { text: "Contraindications: CAD, prior MI, uncontrolled HTN, hemiplegic or basilar migraine, peripheral vascular disease, within 24h of ergot" },
  { text: "Pharmacokinetics table: Frovatriptan — longest t½ (27h); Sumatriptan — fastest SC onset (12 min)" },
  "LASMIDITAN (5-HT1F agonist) — Newer acute migraine (no vasoconstriction → better CV safety)",
  "BUSPIRONE (5-HT1A partial agonist) — Generalised anxiety disorder; non-sedating, non-addictive",
  "Ergotamine & Dihydroergotamine (DHE) — Partial agonist at 5-HT1B/D; also α-adrenergic activity; used in cluster headache & refractory migraine",
]);

contentSlide("Serotonin Antagonists – Clinical Use", [
  "5-HT3 Antagonists (Setrons) — Antiemetics",
  { text: "Ondansetron, Granisetron, Dolasetron, Palonosetron, Alosetron (IBS-D)" },
  { text: "Indications: Chemotherapy-induced & post-op nausea/vomiting; carcinoid-associated diarrhea; IBS-D (alosetron)" },
  { text: "AEs: Constipation, headache; QT prolongation (ondansetron high doses)" },
  "5-HT2 Antagonists — Multiple classes",
  { text: "Cyproheptadine: H1 + 5-HT2 blocker; appetite stimulant, serotonin syndrome (adjunct), carcinoid flush" },
  { text: "Methysergide: 5-HT2 blocker; prophylaxis of cluster headache; AE: retroperitoneal/pleural fibrosis (obsolete)" },
  { text: "Atypical antipsychotics (clozapine, risperidone, olanzapine): Block 5-HT2A/2C → weight gain, improved negative symptoms" },
  "SSRIs — Block SERT → ↑synaptic 5-HT → antidepressant/anxiolytic (fluoxetine, sertraline, escitalopram)",
  "Serotonin Syndrome: ↑5-HT → agitation, hyperthermia, clonus, diaphoresis; Rx: cyproheptadine, benzodiazepines",
]);

// ═══════════════════════════════════════════════════════════════════════════
// SECTION 4 — EICOSANOIDS
// ═══════════════════════════════════════════════════════════════════════════
sectionDivider("04  Eicosanoids", "Prostaglandins · Thromboxanes · Leukotrienes · Lipoxins");

contentSlide("Eicosanoids – Overview & Synthesis", [
  "Eicosanoids: 20-carbon polyunsaturated fatty acid derivatives from arachidonic acid (AA)",
  "AA source: Released from membrane phospholipids by Phospholipase A2 (PLA2) — rate-limiting step",
  "Corticosteroids inhibit PLA2 (via lipocortin/annexin-1) — broadest anti-inflammatory action",
  "Two main pathways from AA:",
  { text: "COX pathway (Cyclooxygenase 1 & 2) → Prostaglandins (PGE2, PGI2, PGD2, PGF2α) + Thromboxanes (TXA2)" },
  { text: "LOX pathway (5-Lipoxygenase + FLAP) → Leukotrienes (LTA4 → LTB4, LTC4, LTD4, LTE4)" },
  "COX-1: Constitutive; housekeeping functions (gastric protection, platelet TXA2, renal blood flow)",
  "COX-2: Inducible by cytokines/injury; mediates inflammation, fever, pain; also found in kidney & brain",
  "Additional pathways: CYP450 epoxygenases, Cytochrome P450 ω-hydroxylase",
]);

contentSlide("Prostaglandins & Thromboxanes", [
  "Prostanoids: PGD2, PGE2, PGF2α, PGI2 (prostacyclin), TXA2 — act on G-protein coupled receptors (DP, EP, FP, IP, TP)",
  "PGE2: Most versatile — fever (hypothalamic EP3), pain sensitization (EP1/EP3 on nociceptors), gastric cytoprotection (EP3 → ↓acid, ↑mucus), renal vasodilation (maintains GFR in low-flow states), smooth muscle contraction/relaxation (tissue specific)",
  "PGI2 (Prostacyclin): From endothelium — vasodilation + ↓platelet aggregation (IP receptor, ↑cAMP); opposes TXA2; Epoprostenol (IV) for pulmonary arterial hypertension",
  "TXA2: From platelets (COX-1) — potent vasoconstriction + platelet aggregation (TP receptor); half-life ~30 sec; blocked by aspirin (irreversible COX-1 acetylation)",
  "PGF2α: Uterine contraction (luteolysis, parturition); IOP reduction in glaucoma (latanoprost — PGF2α analogue)",
  "PGD2: Mast cell product; bronchoconstriction, vasodilation, sleep regulation",
  "Therapeutic prostaglandins: Misoprostol (PGE1 analogue, gastric protection, cervical ripening), Alprostadil (PGE1, erectile dysfunction, ductus arteriosus), Latanoprost (FP agonist, glaucoma)",
]);

contentSlide("Leukotrienes & Lipoxins", [
  "Leukotrienes: Produced mainly by mast cells, basophils, eosinophils, macrophages, neutrophils",
  "LTB4 (dihydroxy-leukotriene): Potent neutrophil chemotaxis & activation; mediates tissue damage in ARDS, IBD, psoriasis",
  "Cysteinyl leukotrienes (CysLTs): LTC4, LTD4, LTE4 — previously known as Slow Reacting Substance of Anaphylaxis (SRS-A)",
  { text: "CysLT1 receptor activation → bronchoconstriction (100× more potent than histamine), ↑mucus secretion, airway edema, eosinophil recruitment" },
  "Leukotriene Receptor Antagonists (LTRAs): Montelukast, Zafirlukast, Pranlukast",
  { text: "Indications: Mild-moderate asthma (add-on), allergic rhinitis, aspirin-exacerbated respiratory disease, exercise-induced bronchospasm" },
  { text: "AEs: Headache, GI upset; rare: Churg-Strauss (eosinophilic granulomatosis with polyangiitis — may unmask with steroid reduction)" },
  "5-LOX Inhibitor: Zileuton — blocks 5-lipoxygenase; requires LFT monitoring (hepatotoxicity)",
  "Lipoxins: Endogenous anti-inflammatory, pro-resolution lipid mediators; limit neutrophil recruitment",
]);

contentSlide("NSAIDs & COX Inhibitors – Mechanisms", [
  "NSAIDs: Inhibit COX-1 and/or COX-2 → ↓prostaglandin synthesis → analgesic, anti-inflammatory, antipyretic effects",
  "Aspirin: Unique — irreversibly acetylates COX-1 (& COX-2) Ser530; low-dose (75–325mg) → antiplatelet; high-dose → anti-inflammatory",
  "Non-selective NSAIDs: Ibuprofen, Naproxen, Diclofenac, Indomethacin, Ketorolac, Piroxicam",
  { text: "AEs: GI ulceration (↓PGE2 → ↓mucosal protection), renal impairment (↓PGE2 → ↓GFR), platelet dysfunction, HTN, hypersensitivity (aspirin-exacerbated asthma)" },
  "Selective COX-2 Inhibitors (Coxibs): Celecoxib, Etoricoxib, Parecoxib",
  { text: "↓GI side effects vs non-selective NSAIDs; but: ↑cardiovascular risk (↓PGI2 without ↓TXA2 → prothrombotic state; Rofecoxib/Vioxx withdrawn)" },
  "Paracetamol (Acetaminophen): Weak COX inhibitor in peripheral tissues; central mechanism via cannabinoid/serotonin system; potent antipyretic/analgesic; overdose → hepatotoxicity (NAPQI accumulation)",
]);

// ═══════════════════════════════════════════════════════════════════════════
// SECTION 5 — KININS
// ═══════════════════════════════════════════════════════════════════════════
sectionDivider("05  Kinins & Kallikrein-Kinin System", "Bradykinin · Kallidin · ACE Inhibitor Link");

contentSlide("Kinins – Synthesis & Mechanism", [
  "Kinins: Short-lived peptides; most potent endogenous pain-producing and vasodilating substances",
  "Main kinins: Bradykinin (BK) — nonapeptide (9 AA); Kallidin (Lys-Bradykinin) — decapeptide",
  "Synthesis pathway:",
  { text: "Plasma prekallikrein → activated by Factor XIIa (Hageman factor) → Plasma kallikrein" },
  { text: "Plasma kallikrein cleaves High-molecular-weight kininogen (HMWK) → Bradykinin" },
  { text: "Tissue (glandular) kallikrein cleaves LMWK or HMWK → Kallidin (Lys-BK)" },
  "Degradation: Kininase I (carboxypeptidase N, in plasma) & Kininase II = ACE (angiotensin-converting enzyme, in lung) — identical to enzyme that converts Ang I → Ang II",
  "ACE inhibitors (captopril, enalapril, lisinopril) block kinin degradation → ↑bradykinin → vasodilation, natriuresis",
  "ACE inhibitor cough: Bradykinin accumulation in airway → stimulates sensory nerves (PGE2 and SP mediated) → dry persistent cough (10-20%); switch to ARB",
  "Hereditary Angioedema (HAE): C1-esterase inhibitor deficiency → ↑bradykinin → episodic angioedema; Rx: C1-INH concentrate, icatibant (B2 antagonist), lanadelumab (anti-kallikrein MAb)",
]);

contentSlide("Bradykinin Receptors & Effects", [
  "B1 receptor: Induced (NOT constitutive); upregulated by tissue injury, cytokines; mediates chronic inflammatory pain; agonist: des-Arg9-BK",
  "B2 receptor: Constitutive; mediates most acute bradykinin effects; agonist: bradykinin, kallidin",
  "Organ effects via B2 (mainly):",
  { text: "Vasodilation: ↑NO (endothelium) + ↑PGI2 → potent vasodilation; ↑vascular permeability → edema" },
  { text: "Pain: Sensitises nociceptors + stimulates free nerve endings (via B1 in chronic pain)" },
  { text: "Bronchoconstriction: Indirect (via PG, histamine release from mast cells) → mild in healthy, pronounced in asthmatics" },
  { text: "Kidney: Natriuresis; renal vasodilation" },
  { text: "GI: Smooth muscle contraction" },
  "B2 antagonist: Icatibant (HOE 140) — approved for HAE acute attacks",
  "Ecallantide: Plasma kallikrein inhibitor — approved for HAE",
  "Clinical relevance: ACE inhibitors utilise bradykinin for part of their antihypertensive + cardioprotective benefit",
]);

// ═══════════════════════════════════════════════════════════════════════════
// SECTION 6 — SUBSTANCE P & NEUROPEPTIDES
// ═══════════════════════════════════════════════════════════════════════════
sectionDivider("06  Neuropeptides & Other Autocoids", "Substance P · CGRP · PAF · Adenosine");

contentSlide("Substance P & CGRP", [
  "Substance P: Undecapeptide (11 AA); member of tachykinin family; found in primary afferent C-fibers, CNS, GI tract",
  "Receptor: Neurokinin-1 (NK1) receptor — Gq coupled",
  "Effects: Neurotransmitter of pain (spinal cord 'wind-up'), neurogenic inflammation, vasodilation, bronchoconstriction, GI motility",
  "NK1 Antagonists (Aprepitant, Fosaprepitant, Netupitant, Rolapitant): Antiemetics for highly emetogenic chemotherapy (HEC/MEC); prevent delayed CINV",
  { text: "Combined regimen: 5-HT3 antagonist + NK1 antagonist + dexamethasone ± olanzapine → standard CINV prophylaxis" },
  "CGRP (Calcitonin Gene-Related Peptide): 37 AA neuropeptide; co-released with Substance P from trigeminovascular fibres",
  { text: "Key role in migraine pathophysiology — potent vasodilator; elevated in jugular venous blood during migraine attacks" },
  { text: "CGRP Antagonists (Gepants): Rimegepant, Ubrogepant, Atogepant — acute & preventive migraine (CV-safe; no vasoconstriction)" },
  { text: "Anti-CGRP/receptor monoclonal antibodies: Erenumab (anti-CGRP receptor), Fremanezumab, Galcanezumab, Eptinezumab — monthly/quarterly SC for migraine prevention" },
]);

contentSlide("Platelet-Activating Factor (PAF) & Adenosine", [
  "PAF: 1-O-alkyl-2-acetyl-sn-glycero-3-phosphocholine — phospholipid autocoid released by platelets, mast cells, basophils, endothelium, macrophages",
  "Receptor: PAFR — Gq/Gi coupled",
  "Effects: Platelet activation & aggregation; bronchoconstriction; ↑vascular permeability; vasodilation at low concentrations; potentiates allergic reactions and anaphylaxis",
  "Role in pathology: Asthma, shock, anaphylaxis, myocardial ischemia, inflammatory bowel disease",
  "PAF antagonists: Rupatadine (dual H1+PAF antagonist); experimental agents (ginkgolide B from Ginkgo biloba)",
  "Adenosine: Purine nucleoside; acts on P1 receptors (A1, A2A, A2B, A3)",
  { text: "A1: ↓HR (negative chronotropy/dromotropy) — used as adenosine IV for SVT cardioversion (bolus dose: 6mg then 12mg)" },
  { text: "A2A: Coronary vasodilation (regadenoson — pharmacologic stress test)" },
  { text: "A2A/A1 antagonists: Methylxanthines (caffeine, theophylline) — bronchodilation, CNS stimulation" },
  "Nitric Oxide (NO): Autocoid produced by NOS from L-Arginine; potent vasodilator; targets soluble guanylate cyclase → ↑cGMP",
]);

// ═══════════════════════════════════════════════════════════════════════════
// SECTION 7 — CLINICAL SUMMARY
// ═══════════════════════════════════════════════════════════════════════════
sectionDivider("07  Clinical High-Yields & Exam Summary", "Key facts & must-know associations");

tableSlide("Drug–Receptor Quick Reference",
  ["Drug / Class", "Target", "Key Indication", "Key AE / Note"],
  [
    ["Diphenhydramine", "H1 blocker (1st gen)", "Allergy, motion sickness, insomnia", "Sedation, anticholinergic"],
    ["Cetirizine / Loratadine", "H1 blocker (2nd gen)", "Allergic rhinitis, urticaria", "Minimal sedation"],
    ["Famotidine", "H2 blocker", "PUD, GERD", "No CYP inhibition"],
    ["Cimetidine", "H2 blocker", "PUD (historical)", "CYP inhibitor, antiandrogenic"],
    ["Sumatriptan", "5-HT1B/D agonist", "Acute migraine", "CI in CAD, vasospasm"],
    ["Ondansetron", "5-HT3 antagonist", "CINV, PONV", "QT prolongation (high dose)"],
    ["Buspirone", "5-HT1A partial agonist", "GAD", "No dependence, slow onset"],
    ["Montelukast", "CysLT1 antagonist", "Asthma, allergic rhinitis", "Rare: neuropsychiatric"],
    ["Aspirin (low-dose)", "Irreversible COX-1", "Antiplatelet (ACS, stroke)", "Bleeding, Reye syndrome"],
    ["Celecoxib", "Selective COX-2", "OA/RA (GI-safe)", "↑CV risk; avoid in sulfa allergy"],
    ["Icatibant", "B2-kinin receptor antagonist", "Hereditary angioedema", "Injection site reactions"],
    ["Aprepitant", "NK1 antagonist", "Delayed CINV", "CYP3A4 inducer + inhibitor"],
    ["Erenumab", "Anti-CGRP receptor MAb", "Migraine prevention", "Constipation, ↑BP"],
    ["Epoprostenol (PGI2)", "IP receptor agonist", "Pulmonary arterial HTN", "Short t½ → continuous IV"],
    ["Misoprostol", "EP1/EP3 agonist", "Gastric protection, labour induction", "Diarrhea, abdominal cramps"],
  ],
  C.bg_mid
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contentSlide("Exam High-Yield Points – Autocoids", [
  "Histamine: ONLY autocoid stored preformed in granules; NOT synthesised on demand",
  "Triple response of Lewis = red line (vasodilation) + flare (axon reflex) + wheal (↑permeability)",
  "H1 = Gq (bronchoconstriction, itch); H2 = Gs (acid secretion); H3 = Gi (autoreceptor); H4 = Gi (eosinophil chemotaxis)",
  "Cimetidine: only H2 blocker that inhibits CYP and causes gynecomastia",
  "Triptans CI in CAD — 5-HT1B activation → coronary vasospasm; Lasmiditan (5-HT1F) is CV-safe",
  "5-HIAA in urine → carcinoid syndrome marker; Telotristat ethyl blocks tryptophan hydroxylase",
  "Serotonin syndrome triad: hyperthermia + autonomic instability + neuromuscular abnormalities; Rx: cyproheptadine",
  "COX-1 = constitutive (gastric protection, platelets); COX-2 = inducible (inflammation, fever)",
  "Aspirin: irreversibly inactivates COX-1 in platelets (no new COX → antiplatelet for 7-10 days)",
  "ACE inhibitor cough → bradykinin accumulation; switch to ARB (which does NOT block kininase II)",
  "Hereditary Angioedema = ↓C1-esterase inhibitor → ↑bradykinin (NOT histamine-mediated → antihistamines ineffective!)",
  "Montelukast: blocks LTD4/LTC4 at CysLT1; useful in aspirin-exacerbated asthma",
]);

contentSlide("Autocoids & Disease Summary", [
  "Anaphylaxis: Histamine (H1/H2) + leukotrienes (CysLT) + PAF; Rx: Epinephrine (1st), antihistamines, corticosteroids",
  "Asthma: CysLTs > histamine; Rx: ICS, β2 agonists, LTRAs (montelukast, zileuton), anti-IL-5",
  "Migraine: CGRP + 5-HT; Rx acute: triptans, gepants, lasmiditan, ergotamines; preventive: anti-CGRP MAbs, topiramate, propranolol",
  "Peptic Ulcer Disease: ↑Histamine (H2) + ↓PGE2 (NSAIDs); Rx: PPIs, H2 blockers, misoprostol (NSAID-associated)",
  "Hereditary Angioedema: ↑Bradykinin; Rx: C1-INH concentrate, icatibant, ecallantide, lanadelumab",
  "Carcinoid Syndrome: Excess 5-HT → flushing, diarrhea, bronchoconstriction, right heart fibrosis; Rx: octreotide, telotristat",
  "Pulmonary Arterial Hypertension: ↓PGI2 + ↑TXA2; Rx: prostacyclin analogues (epoprostenol, treprostinil, iloprost)",
  "Glaucoma: ↑IOP; Rx with PGF2α analogues (latanoprost, bimatoprost) → ↑aqueous outflow",
  "Gout (acute): PGE2, bradykinin, IL-1 mediated inflammation; Rx: NSAIDs, colchicine, corticosteroids",
]);

// ═══════════════════════════════════════════════════════════════════════════
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